Purines are critical biological molecules. They act as the precursors for DNA and RNA synthesis, as major components of cellular energy metabolism, as intracellular second messenger signaling molecules, as extracellular neurotransmitters, and as coenzymes for many critical biochemical reactions. All free-living organisms can synthesize purines. The de novo biosynthetic pathway consists of 10 enzymatic steps resulting in the synthesis of IMP. As might be expected, cancer cells, with their increased requirements for DNA and RNA synthesis, generally have elevated rates of purine synthesis. Therefore, it is not surprising that analogues of purines or molecules that inhibit purine synthesis are common anti-cancer drugs.
Viral infection has long been associated with human cancers. One of the first, and strongest, associations is with Epstein-Barr Virus (EBV), which is an etiologic agent in Burkitt's Lymphoma (BL), Hodgkin's disease, some T-cell lymphomas and nasopharyngeal carcinoma. EBV is a DNA virus that is related to the herpes viruses, and the most recent nomenclature recommendation is that it is renamed human herpes virus 4 (HHV4) (3). Recently, human herpes virus 8 (HHV8) has been strongly implicated as the etiologic agent in Kaposi's sarcoma in AIDS patents. The mechanisms by which EBV viral infection may work are still being clarified. Since viruses put heavy demands on the host DNA and RNA synthesis machinery, it may well be that during viral infection there is an elevated requirement for purine synthesis. Specifically, viruses may alter or assume control of cellular purine metabolism as a part of viral infection. As with cancer, some of the most effective antiviral agents for example, acyclovir, are purine nucleotide analogues. Interestingly, EBV and other viruses appear to possess genes important for nucleotide metabolism including ribonucleotide reductase, dihydrofolate reductase, and thymidine kinase. So far, no reports of viral genes participating directly in purine synthesis have been published.